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Bupivacaine (Liposomal)

Pronunciation

(byoo PIV a kane lye po SO mal)

Index Terms

  • Bupivacaine Liposome
  • Bupivacaine Liposome/Pf
  • DepoFoam Bupivacaine
  • Exparel
  • Liposomal Bupivacaine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension, Injection:

Exparel: 1.3% (20 mL)

Brand Names: U.S.

  • Exparel

Pharmacologic Category

  • Analgesic, Nonopioid

Pharmacology

Blocks both the initiation and conduction of nerve impulses by decreasing the neuronal membrane's permeability to sodium ions, which results in inhibition of depolarization with resultant blockade of conduction.

Metabolism

Hepatic via conjugation; major metabolite pipecoloxylidine (PPX; inactive)

Excretion

Urine (~6% unchanged)

Time to Peak

0.5 to 2 hours

Duration of Action

Local: Systemic: 96 hours

Half-Life Elimination

24 to 34 hours

Protein Binding

95%

Special Populations: Renal Function Impairment

Renal impairment may reduce bupivacaine elimination increasing systemic exposure and the risk of adverse effects or toxicities.

Special Populations: Hepatic Function Impairment

Moderate to severe impairment may reduce bupivacaine metabolism increasing systemic exposure and the risk of adverse effects or toxicities

Use: Labeled Indications

Postsurgical analgesia: Injection into the surgical site to provide postsurgical analgesia.

Contraindications

Obstetrical paracervical block anesthesia

Dosing: Adult

Note: Different formulations of bupivacaine are not bioequivalent even if the mg strength is the same; do not convert dosing from any other bupivacaine formulation to bupivacaine (liposomal).

Postsurgical analgesia: Infiltration (local): Dose is based on size of surgical site, volume required to cover the area, and individual patient factors (maximum dose: 266 mg (20 mL). General dosage guidance for bunionectomy and hemorrhoidectomy provided below:

Bunionectomy: 7 mL of undiluted bupivacaine (liposomal) into the tissues surrounding the osteotomy and 1 mL of undiluted bupivacaine (liposomal) into the subcutaneous tissue of the surgical site (total dose = 106 mg [8 mL])

Hemorrhoidectomy: 30 mL of diluted bupivacaine (liposomal) (20 mL diluted with 10 mL NS) divided and administered as 6 injections of 5 mL each (total dose = 266 mg [20 mL]

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling; however, renal impairment may reduce bupivacaine elimination increasing systemic exposure and the risk of adverse effects or toxicities; use with caution.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling; however, moderate-to-severe impairment may reduce bupivacaine metabolism increasing systemic exposure and the risk of adverse effects or toxicities; use with caution.

Reconstitution

Invert vial several times prior to withdrawing contents to resuspend particles. May dilute with NS or LR up to a final concentration of 0.89 mg/mL (ie, a 1:14 dilution by volume). Use only NS or LR for dilution; use of water or other hypotonic agents will disrupt liposomal particles. Do not admix with other local anesthetics (except for bupivacaine hydrochloride) or drugs.

Administration

Administer undiluted or diluted by local infiltration; inject slowly into soft tissues of the surgical site using a ≥25 gauge needle with frequent aspiration prior to and during administration; do not filter. Do not administer epidurally, intrathecally, intravascularly, intra-articularly, or as a regional nerve block. Invert vial several times prior to withdrawing contents to resuspend particles. Do not allow bupivacaine (liposomal) to come into contact with antiseptics (eg, povidone iodine) in solution; when a topical antiseptic is applied, allow site to dry prior to injection of bupivacaine (liposomal) into the surgical site. Non-bupivacaine-based local anesthetics may cause an immediate release of bupivacaine (liposomal) if administered together locally; may administer bupivacaine (liposomal) ≥20 minutes following administration of local lidocaine. Do not administer other formulations of bupivacaine within 96 hours following bupivacaine (liposomal) administration; bupivacaine hydrochloride may be administered simultaneously in the same syringe or injected immediately before bupivacaine (liposomal) as long as the ratio of bupivacaine dose to bupivacaine (liposomal) dose in mg does not exceed 1:2.

Compatibility

Stable in NS, LR.

Storage

Store intact at 2°C to 8°C (36°F to 46˚F); do not freeze; do not heat or autoclave vials once removed from refrigerator. Intact vials may also be stored at 20°C to 25°C (68°F to 77°F) for up to 30 days (do not re-refrigerate). Following withdrawal from the vial, may be held at 20°C to 25°C (68°F to 77°F) up to 4 hours prior to administration. Do not administer if it is suspected that the vial has been frozen or exposed to high temperature (>40°C [104°F]) for an extended period of time. Discard any unused medication.

Drug Interactions

Bupivacaine: May enhance the adverse/toxic effect of Bupivacaine (Liposomal). Management: Bupivacaine may be administered immediately before, or administered in the same admixture syringe as liposomal bupivacaine as long as the ratio of the milligram dose of bupivacaine to liposomal bupivacaine does not exceed 1:2. Consider therapy modification

Hyaluronidase: May enhance the adverse/toxic effect of Local Anesthetics. Monitor therapy

Lidocaine (Systemic): May enhance the adverse/toxic effect of Bupivacaine (Liposomal). Management: Liposomal bupivacaine should not be administered with topical lidocaine. Liposomal bupivacaine may be administered 20 minutes or more after the administration of lidocaine. Consider therapy modification

Local Anesthetics: May enhance the adverse/toxic effect of Bupivacaine (Liposomal). Management: Liposomal bupivacaine should not be administered with local anesthetics. Liposomal bupivacaine may be administered 20 minutes or more after the administration of lidocaine, but the optimal duration of dose separation for other local anesthetics is unknown Exceptions: Benzocaine; Benzydamine; Cocaine; Dibucaine; Dyclonine; Ethyl Chloride; Hexylresorcinol; Lidocaine (Ophthalmic); Lidocaine (Topical); Pramoxine; Proparacaine; Tetracaine (Ophthalmic); Tetracaine (Topical). Avoid combination

Technetium Tc 99m Tilmanocept: Local Anesthetics may diminish the diagnostic effect of Technetium Tc 99m Tilmanocept. Management: Avoid mixing and simultaneously co-injecting technetium Tc 99m tilmanocept with local anesthetics. This interaction does not appear to apply to other uses of these agents in combination. Monitor therapy

Adverse Reactions

Frequency not always defined.

>10%: Gastrointestinal: Nausea (2% to 40%), vomiting (28%), constipation (2% to ≥10%)

1% to 10%:

Cardiovascular: Hypotension (2% to 10%), peripheral edema (2% to 10%), tachycardia (4%), bradycardia (2%), edema (<2%), hypertension (<2%), palpitations (<2%), sinus bradycardia (<2%), supraventricular extrasystole (<2%), syncope (<2%), ventricular premature contractions (<2%), ventricular tachycardia (<2%), heart block

Central nervous system: Insomnia (2% to 10%), dizziness (6%), drowsiness (2% to 5%), headache (4%), flushing sensation (2%), hypoesthesia (2%), agitation (<2%), anxiety (<2%), chills (<2%), confusion (<2%), depression (<2%), pain (<2%), paresthesia (<2%), restlessness (<2%), lethargy (1%), paralysis, persistent anesthesia, seizure

Dermatologic: Pruritus (3%), diaphoresis (<2%), erythema (<2%), hyperhidrosis (<2%), pallor (<2%), pruritic rash (<2%), urticaria (<2%)

Genitourinary: Urinary incontinence (<2%), urinary retention (<2%)

Hematologic & oncologic: Acute posthemorrhagic anemia (2% to 10%; postoperative)

Hepatic: Increased serum AST (3%), increased serum ALT (1%)

Hypersensitivity: Anaphylactoid reaction (<2%), hypersensitivity reaction (<2%)

Infection: Fungal infection (2%)

Local: Localized edema (incision site: 2%)

Neuromuscular & skeletal: Back pain (2% to 10%), muscle spasm (2% to 10%), laryngospasm (<2%), neck pain (<2%), tremor (<2%), weakness (<2%), chondrolysis (continuous intra-articular administration; develops months after surgery)

Ophthalmic: Blurred vision (<2%), miosis

Otic: Tinnitus (<2%)

Renal: Increased serum creatinine (2%)

Respiratory: Apnea (<2%), hypoxia (<2%), respiratory depression (<2%), respiratory failure (<2%)

Miscellaneous: Fever (2%)

Warnings/Precautions

Concerns related to adverse effects:

• CNS effects: CNS effects (including excitation and/or depression) may occur, possibly leading to convulsions, unconsciousness, and/or respiratory arrest; may be related to total dose administered, route of administration, and physical status of patient; monitor for CNS-related changes or alterations in consciousness after each injection. Additionally, use of local anesthetics have been associated with neurologic effects following infiltration of soft tissue (persistent anesthesia, paresthesia weakness, paralysis), which may be irreversible.

• CNS toxicity: Careful and constant monitoring of the patient's state of consciousness should be done following each local anesthetic injection; at such times, restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, twitching, tinnitus, dizziness, blurred vision, tremors, depression, or drowsiness may be early warning signs of CNS toxicity. Serious and fatal cardiovascular system reactions (eg, decreased cardiac output and arterial blood pressure, atrioventricular block, ventricular arrhythmias, cardiac arrest) may occur with toxic concentrations.

• Hypersensitivity reactions: Allergic-type reactions (eg, angioneurotic edema [including laryngeal edema], dizziness, elevated temperature, excessive sweating, nausea, syncope, tachycardia, pruritus, erythema, sneezing, urticaria, vomiting) and possibly anaphylactoid-like symptoms (including severe hypotension) have been reported (rare); cross-sensitivity among amide-type local anesthetics has been reported.

• Intra-articular infusion related chondrolysis: Continuous intra-articular infusion of local anesthetics after arthroscopic or other surgical procedures is not an approved use; chondrolysis (primarily in the shoulder joint) has occurred following infusion, with some cases requiring arthroplasty or shoulder replacement.

• Respiratory arrest: Local anesthetics have been associated with rare occurrences of sudden respiratory arrest.

• Seizures: Convulsions due to systemic toxicity leading to cardiac arrest have been reported with local anesthetics.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease; patients with impaired cardiovascular function are less able to compensate for functional changes associated with AV conduction prolongation produced by bupivacaine.

• Hepatic impairment: Use with caution in patients with hepatic impairment; patients with severe impairment may be at greater risk for toxicity.

• Renal impairment: Use with caution in patients with renal impairment; may be at greater risk for toxicity.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: Avoid intravascular, epidural, intrathecal, intra-articular, and regional nerve block injections. Not indicated used for preincisional or preprocedural locoregional anesthetic techniques that require deep and complete sensory block. Aspiration should must be performed frequently prior to and during administration; the needle must be repositioned until no return of blood can be elicited by aspiration; however, absence of blood in the syringe does not guarantee that intravascular injection has been avoided.

• Product interchangeability: Different formulations of bupivacaine are not bioequivalent even if the mg strength is the same; do not convert dosing from any other formulations of bupivacaine to bupivacaine (liposomal) and vice versa.

• Trained personnel: Clinicians using local anesthetic agents should be well trained in diagnosis and management of emergencies that may arise from the use of these agents. Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use.

Monitoring Parameters

Cardiovascular and respiratory (adequacy of ventilation) vital signs, state of consciousness; signs of CNS toxicity, pain relief.

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Bupivacaine crosses the placenta. Not recommended for use in pregnancy. Use in obstetrical paracervical block anesthesia is contraindicated; may cause fetal bradycardia and death.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, insomnia, muscle spasms, or back pain. Have patient report immediately to prescriber agitation, anxiety, change in speech, severe dizziness, passing out, metallic taste, tinnitus, blurred vision, tremors, twitching, depression, fatigue, seizures, nausea, vomiting, chills, mitosis, angina, tachycardia, abnormal heartbeat, sneezing, sweating a lot, joint pain, joint rigidity, change in balance, weakness, numbness, or tingling, swelling of arms or legs, or severe loss of strength and energy (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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